scholarly journals Applying polygenic risk scoring for psychiatric disorders to a large family with Bipolar Disorder and Major Depressive Disorder

2017 ◽  
Author(s):  
Simone de Jong ◽  
Mateus Jose Abdalla Diniz ◽  
Andiara Calado Saloma Rodrigues ◽  
Ary Gadelha ◽  
Marcos L Santoro ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Psychiatric Disorders ◽  
Risk Scores ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Common Variation ◽  
The Family ◽  
Risk Scoring

ABSTRACTWe aim to investigate the application of polygenic risk scoring within a family context. Polygenic risk profiles could aid in unraveling the role that common variation confers on disease risk within a pedigree that would have traditionally been viewed through the prism of monogenic inheritance only. We illustrate our discussion by analyzing polygenic risk scores for schizophrenia, major depressive disorder and bipolar disorder in a large pedigree (n~260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. We apply polygenic risk scores to study patterns of assortative mating and anticipation, whereby it appears increased polygenic risk for psychiatric disorders is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations in the family. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity of a disease increases over the generations of a family. Joint analyses of both rare and common variation may be the most powerful way to understand the familial genetics of mood and psychiatric disorders.

scholarly journals Polygenic interactions with environmental adversity in the aetiology of major depressive disorder

2015 ◽  
Vol 46 (4) ◽  
pp. 759-770 ◽  
Author(s):  
N. Mullins ◽  
R. A. Power ◽  
H. L. Fisher ◽  
K. B. Hanscombe ◽  
J. Euesden ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Environmental Risk ◽  
Complex Traits ◽  
Risk Scores ◽  
Environment Interaction ◽  
Inverse Association ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Gene Environment

BackgroundMajor depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p= 1.9 × 10−6). SLEs and CT were also associated with MDD status (p= 2.19 × 10−4andp= 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p= 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.

P01-331-Family functioning of adolescents with a major depressive disorder – a comparative study

2011 ◽  
Vol 26 (S2) ◽  
pp. 333-333
Author(s):  
M.L. Perereira ◽  
D.L. Nunes Peçanha ◽  
I.A. Santos Bordin
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Family Functioning ◽  
Psychiatric Disorders ◽  
Family Income ◽  
Well Being ◽  
Occupational Activity ◽  
Major Depressive ◽  
The Family ◽  
Depressive Episodes

IntroductionPsychiatric disorders occur in a complex context of human relations in its social and psychological aspects. Family functioning is closely related to physical and psychological well-being of family members and its impairment affects the family as a whole.ObjectivesTo evaluate family functioning in two groups of adolescents (13–18 years): cases (with major depressive disorder) and controls (with no DSM-IV psychiatric disorders based on the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime/K-SADS-PL).MethodFamilies of cases (N = 9) and controls (N = 9) were matched by adolescent's age, gender and education, number and age of siblings, parental marital status and occupational activity, and family income. An experienced systemic family therapist applied the Structured Family Interview to each family. Nine dimensions of family functioning were evaluated: communication, rules, roles, leadership, conflict, aggressiveness, affect, individuation and integration. Session transcripts were independently evaluated by two other systemic family therapists blind to the family case-control category.ResultsRaters scored all interview items using a standardized coding system (overall agreement = 83.5%). Cases exhibited lower mean scores in seven family dimensions, specially affect (p = 0.0078). Differences were not found regarding rules and leadership.ConclusionDifficulty in expressing affect in parent-child relationships was the main characteristic of families with a depressive adolescent. Improvement of family functioning can contribute to minimize the negative influence of psychosocial and family factors on the reoccurrence, and severity of depressive episodes among depressed adolescents.

Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder

2017 ◽  
Vol 39 ◽  
pp. 51-56 ◽  
Author(s):  
K. Hamazaki ◽  
M. Maekawa ◽  
T. Toyota ◽  
B. Dean ◽  
T. Hamazaki ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Fatty Acid ◽  
White Matter ◽  
Corpus Callosum ◽  
Depressive Disorder ◽  
Psychiatric Disorders ◽  
Postmortem Brain ◽  
Major Depressive

AbstractBackgroundStudies investigating the relationship between n-3 polyunsaturated fatty acid (PUFA) levels and psychiatric disorders have thus far focused mainly on analyzing gray matter, rather than white matter, in the postmortem brain. In this study, we investigated whether PUFA levels showed abnormalities in the corpus callosum, the largest area of white matter, in the postmortem brain tissue of patients with schizophrenia, bipolar disorder, or major depressive disorder.MethodsFatty acids in the phospholipids of the postmortem corpus callosum were evaluated by thin-layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n = 15), bipolar disorder (n = 15), or major depressive disorder (n = 15) and compared with unaffected controls (n = 15).ResultsIn contrast to some previous studies, no significant differences were found in the levels of PUFAs or other fatty acids in the corpus callosum between patients and controls. A subanalysis by sex gave the same results. No significant differences were found in any PUFAs between suicide completers and non-suicide cases regardless of psychiatric disorder diagnosis.ConclusionsPatients with psychiatric disorders did not exhibit n-3 PUFAs deficits in the postmortem corpus callosum relative to the unaffected controls, and the corpus callosum might not be involved in abnormalities of PUFA metabolism. This area of research is still at an early stage and requires further investigation.

scholarly journals Dissection of major depressive disorder using polygenic risk scores for schizophrenia in two independent cohorts

2016 ◽  
Vol 6 (11) ◽  
pp. e938-e938 ◽  
Author(s):  
H C Whalley ◽  
M J Adams ◽  
L S Hall ◽  
T-K Clarke ◽  
A M Fernandez-Pujals ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Risk Scores ◽  
Major Depressive ◽  
Polygenic Risk

Discriminating bipolar depression from major depressive disorder with polygenic risk scores

2020 ◽  
pp. 1-8 ◽  
Author(s):  
David T. Liebers ◽  
Mehdi Pirooznia ◽  
Andrea Ganna ◽  
Fernando S. Goes ◽  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Clinical Features ◽  
Clinical Symptoms ◽  
Bipolar Depression ◽  
Risk Scores ◽  
Characteristic Analysis ◽  
Major Depressive ◽  
Polygenic Risk ◽  
Increased Risk

Abstract Background Although accurate differentiation between bipolar disorder (BD) and unipolar major depressive disorder (MDD) has important prognostic and therapeutic implications, the distinction is often challenging based on clinical grounds alone. In this study, we tested whether psychiatric polygenic risk scores (PRSs) improve clinically based classification models of BD v. MDD diagnosis. Methods Our sample included 843 BD and 930 MDD subjects similarly genotyped and phenotyped using the same standardized interview. We performed multivariate modeling and receiver operating characteristic analysis, testing the incremental effect of PRSs on a baseline model with clinical symptoms and features known to associate with BD compared with MDD status. Results We found a strong association between a BD diagnosis and PRSs drawn from BD (R2 = 3.5%, p = 4.94 × 10−12) and schizophrenia (R2 = 3.2%, p = 5.71 × 10−11) genome-wide association meta-analyses. Individuals with top decile BD PRS had a significantly increased risk for BD v. MDD compared with those in the lowest decile (odds ratio 3.39, confidence interval 2.19–5.25). PRSs discriminated BD v. MDD to a degree comparable with many individual symptoms and clinical features previously shown to associate with BD. When compared with the full composite model with all symptoms and clinical features PRSs provided modestly improved discriminatory ability (ΔC = 0.011, p = 6.48 × 10−4). Conclusions Our study demonstrates that psychiatric PRSs provide modest independent discrimination between BD and MDD cases, suggesting that PRSs could ultimately have utility in subjects at the extremes of the distribution and/or subjects for whom clinical symptoms are poorly measured or yet to manifest.

Clock gene polygenic risk score and seasonality in major depressive disorder and bipolar disorder

2020 ◽  
Vol 19 (8) ◽  
Author(s):  
Alex Ferrer ◽  
Javier Costas ◽  
Mònica Gratacos ◽  
Èrika Martínez‐Amorós ◽  
Javier Labad ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Risk Score ◽  
Clock Gene ◽  
Polygenic Risk Score ◽  
Major Depressive ◽  
Polygenic Risk
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